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The Wnt/JNK signaling target gene alcam is required for embryonic kidney development

机译:Wnt / JNK信号传导靶基因alcam是胚胎肾脏发育所必需的

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Proper development of nephrons is essential for kidney function. β-Catenin-independent Wnt signaling through Fzd8, Inversin, Daam1, RhoA and Myosin is required for nephric tubule morphogenesis. Here, we provide a novel mechanism through which non-canonical Wnt signaling contributes to tubular development. Using Xenopus laevis as a model system, we found that the cell-adhesion molecule Alcam is required for proper nephrogenesis and functions downstream of Fzd3 during embryonic kidney development. We found alcam expression to be independent of Fzd8 or Inversin, but to be transcriptionally regulated by the β-Catenin-independent Wnt/JNK pathway involving ATF2 and Pax2 in a direct manner. These novel findings indicate that several branches of Wnt signaling are independently required for proximal tubule development. Moreover, our data indicate that regulation of morphogenesis by non-canonical Wnt ligands also involves direct transcriptional responses in addition to the effects on a post-translational level.
机译:肾单位的正常发育对于肾功能至关重要。肾小管形态发生需要通过Fzd8,Inversin,Daam1,RhoA和肌球蛋白的不依赖β-Catenin的Wnt信号传导。在这里,我们提供了一种新的机制,通过该机制,非规范的Wnt信号有助于肾小管发育。使用非洲爪蟾作为模型系统,我们发现细胞粘附分子Alcam是胚胎肾脏发育过程中适当的肾生成和Fzd3下游功能所必需的。我们发现alcam表达独立于Fzd8或Inversin,但受到涉及ATF2和Pax2的β-Catenin独立的Wnt / JNK途径的直接调控。这些新发现表明,近端肾小管发育独立需要Wnt信号的几个分支。此外,我们的数据表明,非经典Wnt配体对形态发生的调控,除了对翻译后水平的影响外,还涉及直接转录反应。

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